Interactions between T cells and antigen-presenting cells involve a variety of accessory molecules that facilitate in the generation of an immune response. One such molecule is CD27, which binds CD70 and belongs to the tumor necrosis factor receptor (TNF-R) superfamily (Ranheim E A, et al., Blood. 1995 Jun. 15; 85(12):3556-65). CD27 typically exists as a glycosylated, type I transmembrane protein, frequently in the form of homodimers with a disulfide bridge linking the two monomers. The disulfide bridge is in the extracellular domain close to the membrane (Camerini et al., J. Immunol. 147:3165-69 (1991). CD27 may also be expressed in a soluble form (see, e.g., van Oers M H, et al., Blood. 1993 Dec. 1; 82(11):3430-6 and Loenen W A, et al., Eur. J. Immunol. 22:447, 1992). Cross-linking the CD27 antigen on T cells provides a costimulatory signal that, in concert with T-cell receptor crosslinking, can induce T-cell proliferation and cellular immune activation.
CD27 is expressed on mature thymocytes, on most CD4+ and CD8+ peripheral blood T cells, natural killer cells and B cells (Kobata T, et al., Proc. Natl. Acad. Sci. USA. 1995 Nov. 21; 92(24):11249-53). CD27 is also highly expressed on B cell non-Hodgkin's lymphomas and B cell chronic lymphocytic leukemias (Ranheim E A, et al., Blood. 1995 Jun. 15; 85(12):3556-65). Additionally, increased levels of soluble CD27 protein have been identified in sera or sites of disease activity in parasitic infection, cytomegalovirus (CMV) infection, sarcoidosis, multiple sclerosis, and B-cell chronic lymphocytic leukemia (Loenen W A, et al., Eur. J. Immunol. 22:447, 1992).
Agonistic monoclonal antibodies against CD27 have recently been shown to promote T cell responses and show promise as anti-cancer therapeutics (see e.g., Sakanishi T, et al., Biochem Biophys. Res. Commun. 2010 Feb. 18 and WO 2008/051424). However, while the results obtained to date establish CD27 as a useful target for immunotherapy, it is unknown which particular features of anti-CD27 monoclonal antibodies are especially advantageous for therapeutic purposes. As such, there is a need in the art for further insight into the specific functional properties that make anti-CD27 antibodies therapeutically effective, as well as improved therapeutic antibodies against CD27 which are more effective for treating and/or preventing diseases.